Dott. M. M. Ciammaichella
Dirigente Medico
SC Medicina Interna I° per l'Urgenza
(Direttore: Dott. G. Cerqua)
A.C.O. S. Giovanni – Addolorata, Roma, Italia

KEY-WORDS: Hypernatremia

INTRODUCTION
CLINICAL
WORKUP
TREATMENT
MEDICATION
FOLLOW-UP
MISCELLANEOUS
BIBLIOGRAPHY

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INTRODUCTION

Background: Hypernatremia, defined as a serum sodium > 145 mEq/L, is a common electrolyte problem, especially in elderly and hospitalized patients. Normally, the serum sodium and serum tonicity is maintained within a relatively narrow range. This occurs via stimulation of thirst and control of renal excretion of water by vasopressin release.
Overall, an intact thirst mechanism with free access to water is the most important factor in preventing hypernatremia.
Given the high mortality (generally reported > 50% in elderly patients) associated with this condition, it is important for the emergency physician to recognize, understand and be able to treat this condition.
Hypertonicity is defined as increased solutes in extracellular fluid (ECF) which do not cross cell membranes (e.g., sodium, mannitol, glucose).
Hyperosmolarity is defined as increased solutes (e.g., urea, alcohol) which freely cross all membranes or glucose which does not cross cell mambranes. It may be present without hypertonicity.

Pathophysiology: Disorders of sodium are the result of a problem with water balance.
Water homeostasis results from the balance between water intake and the combined loss of water from renal excreation, respiratory, skin and gastrointestinal tract sources. Under normal conditions, water intake and losses are matched.
Thirst is physiologically regulated, responding to changes in serum tonicity and extracellular volume. Overall, thirst is the major defense against hypertonicity and in those patients that develop hypernatremia, the major defect is usually impairment of water intake. Even in patients with diabetes insipidus (a condition in which renal water excretion is maximal, up to 20 L/day), dehydration will not occur if the patient has free access to water.
Hypertonicity is a condition in which cells are dehydrated as a result of water loss or an increase in serum osmolarity. The central nervous system is the most important organ system affected by hypernatremia and accounts for most of the symptoms.
Initially the brain cells shrink from water extraction. This is immediately offset by active transport of electrolytes (Na+ and K+) across the neuronal cell membrane. After one hour of hypernatremia, the neurons begin to generate intracellular organic solutes that protect the neurons from structural damage and restore cell volume. This, however, leads to ineffective functioning of the neurons.
This protective mechanism must be kept in mind when treating a patient with hypernatremia. Otherwise, water replacement may proceed at a rate that does not allow for excretion of accumulated solutes, leading to cerebral edema.

Frequency:

Mortality/Morbidity: Overall mortality rates are between 40 and 50%. The highest are among the elderly.

Sex: Male = Female

Age:

• The severity of symptoms usually correlate with the extent of the hyperosmolarity.

• Thirst

• Restlesness

• Irritability

• Disorientation

• Dry mouth

• Fever

• Hyperpyrexia

• Hyperventilation

• Flushed skin

• Oliguria/anuria

• Hyperreflexia

• Muscle twitching Delirium Coma

• Spasticity

• Decreased mental status

• Delirium

• Coma

• Hypovolemic Hypernatremia (Water Deficit > Sodium Deficit):

• Extrarenal Losses:
  
  Diarrhea, vomiting, fistulas, significant burns

• Renal Losses:
  
  Osmotic diuresis, diuretics, postobstruction, intrinsic renal disease

• Hypervolemic Hypernatremia (Sodium Gains > Water Gains):

• Hypertonic saline, NaHCO3 administration, accidental salt ingestion

• Mineralocorticoid excess (Cushing syndrome)

• Euvolemic Hypernatremia:

• Extrarenal Losses:
  
  
• Increased insensible loss (e.g., hyperventilation)
  
  
• Renal Losses:
  
  Central diabetes insipidus, nephrogenic diabetes insipidus

• These patients appear euvolemic because most of the free water loss is from the intracellular and interstitial spaces, with only 8% occurring from the intravascular space. This typically does not produce symptoms unless the serum sodium is > 160 to 170 mEq/L.

• Adipsic hyponatremia is secondary to decreased thrist

• Primary hypodipsia, due to destruction of the thirst centers in the hypothalamus, is a rare cause.

• Essential hypernatremia results from an upward setting of the osmotic threshold for thirst and vasopressin release.

• Adipsic Dypernatremia Differential Diagnosis:
  
  Vascular: (15%) Anterior Communicating Artery (aneurysm, ligation), intrahypothalmic hemorrhage, internal carotid artery ligation
  
  Neoplastic: (50%) Primary, metastatic
  
  Granuloma: (20%) Histocytosis X, sarcoidosis
  
  Miscellaneous: (15%) Hydrocepahlus, ventricular cyst, trauma, idiopathic

• Central Diabetes Insipidus Differential Diagnosis:
  
  Primary or idiopathic (most common cause)
  
  Nonfamilial form, congenital form
  
  Secondary: Head trauma, posthypophysectomy, supracellar or intracellar tumors, granulomas (sarcoidosis, Wegener's granulomatosis, tuberculosis, syphilis), histocytosis (eosinophilc granuloma), infectious (encephalitis, meningits, Guillain-Barre syndrome), vascular (cerebral anerysm, thrombosis, hemorrhage, Sheehan's syndrome)

• Nephrogenic Diabetes Insipidus Differential Diagnosis:
  
  Advanced renal disease (insterstitial disease)
  
  Electrolyte disturbances: hypokalemia, hypercalcemia
  
  Systemic Diseases:
  
  Sickle cell disease, Sjogren's syndrome, amyloidosis, Fanconi sydrome, sarcoidosis, renal
  tubular acidosis, light chain nephropathy
  
  Dietary disturbances: excessive water intake, decreased salt intake, decreased protein intake
  
  Drugs: Lithium, democlocycline, colchicine, vinblastin, amphotericin B, gentamicin, furosemide, angiographic dyes, osmotic diuretics
  
  Miscellaneous: Postobstructive diuresis, diuretic phase of acute renal failure, osmotic diuresis, paroxysmal hypertension

• A low urine sodium and a high urine osmolality is consistent with extrarenal hypotonic fluid losses.

• Isotonic urine osmolality can be seen with diuretics, osmotic diuresis or salt wasting.

• If the serum sodium is > 150-170 mEq/L, it is usually dehydration

• If the serum sodium is > 170 mEq/L is is usually diabetes insipidus

• If the serum sodium is > 190 mEq/L it is usually chronic salt ingestion

• Diabetes Insipidus:

• The urine osmolality is less than the serum osmolality.

• The urine sodium is usually low.

• Pyuria

• Hyperosmolar Coma:

• The blood sugar is elevated.

• Decreased urine output

• Increased urine osmolality

• Chronic Salt Ingestion:

• Increased urine sodium

• Increased urine osmolality

• Hypertonic Dehydration:

• Decreased urine sodium

• Increased urine osmolality

• Head CT Scan or Magnetic Resonance Imaging (MRI):

• Traction on the dural veins and sinuses can lead to intracranial hemorrage.

• May indicate a central cause for the hypernatremia

• To rule out craniopharyngioma, tumor or meian cleft syndrome

• Water Deprivation Test:
  
  With diabetes insipidus, the urine osmolality does not increase with hypernatremia.

• Antidiuretic Hormone (ADH) Stimulation:
  
  With nephrogenic diabetes insipidus, the urine osmolality does not increase after ADH of DDAVP (Desmopressin).
  
  
  
  

• Hypovolemic patients should first be stabilized with normal saline prior to correcting free fluid deficits.
  
  Hypervolemic patients require removal of excess sodium, which can be accomplished by a combination of diuretics and D5W infusion but may require dialysis in the face of ARF.
  Euvolemic patients can be treated with D5W infusions to correct free fluid deficits as calculated below:

• Fluid Deficits:
  
  Free H2O deficit = Body wt (Kg) x %Total body water x (plasma Na/140 ­ 1)
  
  % Total Body Water should be as follows:
  
  0.5 for young women
  
  0.6 for young men
  
  0.4 for elderly women
  
  0.5 for elderly men

• Examples:
  
  A serum sodium (Na) of 155 in a 60 kg young man results in a fluid deficit of
  60 x 0.6 x (155/140 ­ 1) or 3.86 L
  
  A serum sodium of 155 in a 60 kg elderly female results in a fluid deficit of
  60 x 0.4 x (155/140 ­ 1) or 2.57 L

• Replace deficits over 48 hours, allowing for no more than 1 ­ 2 mEq/hr reduction in serum sodium.

• Replacement fluid should be D5W or hypotonic saline (1/4 or 1/2 NS)

• Measure serum electrolytes frequently, initially every two hours.

• Search for and treat the underlying medical condition.

• Replace ongoing fluid losses.

• Dialysis, particularly with serum sodium > 220 mEq/L

• Patients with renal failure may require dialysis to help correct sodium and fluid balance.

• Frequent re-examinations

• Monitor electrolytes frequently.

• Insure that adequate calories are ingested.

• Daily weights

• Patients who are fluid overloaded with hypernatremia may require hemodialysis. These patients should be transferred, if necessary, to a center with hemodialysis availability.

• Treatment of prevention of underlying cause

• Avoid preparing infant formulat at home and never add salt to any commercial infant formula

• Acute hypernatremia often results in significant brain shrinkage causing mechanical traction of cerebral vasculature.

• Stretching of briding veins can result in subdural hemorrhages.

• Venous congestion can lead to venous or sinus thrombosis.

• Arterial stretching can result in subcortical hemorrhages and cerebral infarctions.

• Seizures

• Mental retardation

• Hyperactivity

• Chronic duration (i.e., longer than two days) has a higher mortality

• Patients with a serum sodium greater than 180 mEq/L often have residual central nervous system damage.

• Most patients recover.

• Permanent neurologic sequelae have been reported in 10-30% of patients with acute hypernatremia.

• Since elderly patients are often affected, education of care takers in ways to avoid dehydration may be useful.
  
  
• Patients with nephrogenic diabetes insipidus must avoid salt and drink large amounts of water.